Protein catabolism and protein synthesis in perfused livers of normal and alloxan-diabetic rats.

Profound changes in protein metabolism noted in diabetes mellitus are grossly reflected in a negative nitrogen balance. It is not clear whether this is due to depressed protein synthesis or to increased protein catabolism. Turnover studies with N15glycine have been interpreted to favor an effect on synthesis (1). Krahl (2) has demonstrated that liver slices from diabetic rats have a decreased capacity to incorporate glycine-l-Cl4 into glutathione and into liver proteins. Forker et al. (3), found a 3to 5-fold decrease in the incorporation of Sa5-methionine into muscle proteins of eviscerated depancreatized dogs. Forker and Chaikoff (4) failed to find any abnormality in the rate of degradation of Ss5-methionine-labeled plasma proteins in depancreatized dogs. This report describes isolated liver perfusions in which the net catabolism of leucine-C14-labeled liver and plasma proteins was estimated by the extent of conversion to C?402. The experiments were motivated by the prior observations of Haft and Miller (5, 6) that isolated perfused alloxan-diabetic rat livers have an abnormally large endogenous urea nitrogen production. In brief, this report indicates that the increased urea-nitrogen production in alloxan diabetes may be accounted for by enhanced catabolism of both liver and plasma proteins. Furthermore, incorporation by the alloxan-diabetic liver of uniformly labeled L-leucine-Cl4 into plasma and liver proteins is markedly depressed. The data also demonstrate that diabetic and normal rat livers catabolize the free amino acids m-leucine-l-Cl4 and uniformly labeled L-leucine-C14 to Cl402 at a similar rate, although quantitatively the extent of oxidation of m-leucine-l-C?4 is about three times as great as the extent of oxidation of uniformly labeled n-leucine-C14.